Promotion of myofibroblast differentiation through repeated treatment of fibroblasts to low concentrations of PM2.5

通过反复用低浓度的PM2.5处理成纤维细胞来促进肌成纤维细胞分化

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作者:Nathan A Craig, Anne M Scruggs, Jack P Berens, Furong Deng, Yahong Chen, J Timothy Dvonch, Steven K Huang

Abstract

Exposure to particulate matter ≤ 2.5 µm (PM2.5) is a risk factor for many lung diseases. Although the toxicologic effects of PM2.5 on airway epithelium are well-described, the effects of PM2.5 on fibroblasts in the lung are less studied. Here, we sought to examine the effects of PM2.5 on the differentiation of fibroblasts into myofibroblasts. Although a single treatment of fibroblasts did not result in a change in collagen or the myofibroblast marker α-SMA, exposing fibroblasts to sequential treatments with PM2.5 at low concentrations caused a robust increase in these proteins. Treatment of fibroblasts with IMD0354, an inhibitor to nuclear factor κB, but not with an antagonist to aryl hydrocarbon receptor, abolished the ability of PM2.5 to induce myofibroblast differentiation. These data demonstrate that potential impact of PM2.5 to fibroblast activation and fibrosis and support the importance of utilizing low concentrations and varying exposure protocols to toxicologic studies.

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